Type 2 diabetes (T2D) is highly prevalent in the US with higher prevalence in the minority populations (9-15.9%) as compared to non-Hispanic whites (7.6%). Efforts from large multi- ancestry consortia using genome-wide association studies (GWAS) and next generation sequencing approaches have successfully identified a large number of common and low frequency genetic variants associated with T2D. However, the majority of disease heritability remains unexplained and identification and characterization of the respective causal variants is limited. This project aims to use multi-ancestry GWAS meta-analysis complemented with novel analytical approach, as well as phenomic studies in well-characterized samples to achieve the following specific aims. Aim 1: Discovery and fine mapping of T2D loci using GWAS imputed to ancestry-specific reference panels for trans-ancestry GWAS meta-analysis. Aim 2: Targeted gene-gene and gene-environment interaction to identify novel T2D loci for trans-ancestry GWAS meta-analysis. Aim 3: Integrative Phenomics analyses of comprehensively characterized datasets using clinical metabolic, genomics, transcriptomics, and metabolomics for functional characterization of variants and loci associated with T2D.